<p>The objective of the work was to design a novel felbinac transdermal patch to improve its transdermal delivery efficiency by adding chemical penetration enhancers. The adhesion properties and <i>in vitro</i> transdermal release performance were first evaluated. The transdermal stability and skin irritation were then evaluated. Moreover, <i>in vivo</i> tissue distribution was also examined. The novel felbinac transdermal patch with high adhesion was prepared by calendar coating method. Different types of chemical enhancers and their amount on <i>in vitro</i> transdermal delivery efficiency were systematically screened. <i>In vitro</i> transdermal release experiments showed that by adding 1% propylene glycol (PG) as penetration enhancers, the cumulative transdermal amount of the transdermal patch within 12&#xa0;h was 189.03&#xa0;μg/cm², which was twice that of commercial product SELTOUCH® (94.44&#xa0;μg/cm²). In addition, the transdermal patch still maintained stable permeability after being stored at room temperature for 4&#xa0;months and also had good safety. Further, <i>in vivo</i> experiments confirmed that the concentration of felbinac in plasma, skin, and muscle tissues was significantly increased following administration of the self-made transdermal patch compared to SELTOUCH®. In conclusion, the felbinac transdermal patch developed in this study demonstrated high adhesion, excellent transdermal delivery efficiency and good stability, representing a transdermal drug delivery system with great clinical application potential.</p> Graphical Abstract <p></p>